The experiments described in this proposal aim to contribute specifically to an understanding of hepatocyte specific gene control. Experiments are described that are aimed both at the signals that trigger and maintain liver-specific expression and the nuclear factors that play a direct role in coordinated hepatocyte expression of a number of genes (al anti- trypsin, transthyretin, albumin and others). In addition to specific expression of some genes in all hepatocytes we will study how certain hepatocytes that are geographically localized for example around the central vein produce particular mRNAs that other hepatocytes do not produce. This kind of information should have wide application in questions related to specific gene expression in other tissues and to specific gene expression during development as well. A fundamental understanding of the mechanisms of normal gene regulation in growing, developing and differentiated cells is widely believed, a belief we share, to be necessary to understand many medical problems including cancer.